Lawesson's reagent → (+/-)-(4R,5R)-5-((1S*)-hydroxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-thione

HRID 1837985Notes

Reaction equation

[OH:1][C@H:2]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=O)[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1.COC1C=CC(P2(=S)CP(=S)(C3C=CC(OC)=CC=3)S2)=CC=1>COCCOC>[OH:1][C@H:2]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[S:30])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 65 °C

Procedure

(±)-(4R*,5R*)-5-((1S*)-Hydroxy-2-thienylmethyl)-1-methyl-4-phenyl-pyrrolidin-2-one (Example 5, 0.30 g, 1.06 mmol) and Lawesson's Reagent ([2,4-bis(4-methoxyphenyl)-1,2-dithia-2,4-diphosphetane-2,4-disulfide; 0.22 g, 0.53 mmol) were mixed in DME (3 mL) at rt for 18 h then heated to 65° C. for another 18 h. The reaction was cooled to rt and the solvent was concentrated under reduced pressure to give a dark oil. The crude product was purified by flash chromatography (1% MeOH/99% CH2Cl2) to give (±)-(4R*,5R*)-5-((1S*)-hydroxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-thione (46 mg, 15% yield) as a yellow solid; TLC (75% EtOAc/25% hexanes) Rf 0.36; HPLC ES-MZ m/z (rel abundance) 304 ([MH]+, 100%) AT 4.8 min.

Workup

temperatureThe reaction was cooled to rt
concentrationthe solvent was concentrated under reduced pressure
customto give a dark oil
customThe crude product was purified by flash chromatography (1% MeOH/99% CH2Cl2)

Sources & evidence

ORD record: ord-44e800910464459e9764844756938077
Source dataset: uspto-grants-2004_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06784167B2

Reaction notes

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